[Medication errors reporting in drug clinical trials: Role of the clinical research pharmacist?] / Déclaration des erreurs médicamenteuses dans les recherches portant sur le médicament : place du pharmacien des essais cliniques ?

The investigational drugs circuit has specific risks, and medication errors may occur in clinical trials, possibly associated with adverse reactions. These risks must therefore be managed. In fact, there are few reports of medication errors during clinical trials. In a context of regulatory interpretation difficulties on this subject, we conducted a national survey that highlighted the heterogeneity of the methods used by academic sponsors to collect, code and report medication errors and the need to develop a culture of reporting these errors in clinical trials. This is why the REVISE group (safety officers of French institutional sponsors) has issued recommendations to clarify the sponsor and investigator responsibilities and guide them in the management of medication errors. These new guidelines recommend that any serious or potentially serious medication error or other "special situation" (e.g. overdose, misuse, quality defect) should be notified immediately to the sponsor by the investigator. The clinical research pharmacist place is strategic to detect medication errors and other special situations. The integration of the pharmacist into the reporting system, in collaboration with the investigator, could be discussed with clinical research professionals and health authorities.

Forgiveness of Dolutegravir-Based Triple Therapy Compared With Older Antiretroviral Regimens: A Prospective Multicenter Cohort of Adherence Patterns and HIV-RNA Replication.

BACKGROUND: For many people with HIV (PWH), taking antiretroviral therapy (ARV) every day is difficult. METHODS: Average adherence (Av-Adh) and log-transformed treatment interruption (TI) to ARV were prospectively measured over 6 months using electronic drug monitoring (EDM) in several cohorts of PWH. Multivariate linear regression models including baseline confounders explored the influence of EDM-defined adherence (R 2) on 6-month log10 HIV-RNA. Multivariate logistic regression models were used to compare the risk of HIV-RNA detection (VR) within subgroups stratified by lower (≤95%) and higher (>95%) Av-Adh. RESULTS: Three hundred ninety-nine PWH were analyzed with different ARVs: dolutegravir (n = 102), raltegravir (n = 90), boosted PI (bPI; n = 107), and NNRTI (n = 100). In the dolutegravir group, the influence of adherence pattern measures on R 2 for HIV-RNA levels was marginal (+2%). Av-Adh, TI, and Av-Adh × TI increased the R 2 for HIV-RNA levels by 54% and 40% in the raltegravir and bPI treatment groups, respectively. TI increased the R 2 for HIV-RNA levels by 36% in the NNRTI treatment group. Compared with the dolutegravir-based regimen, the risk of VR was significantly increased for raltegravir (adjusted odds ratio [aOR], 45.6; 95% CI, 4.5-462.1; P = .001), NNRTIs (aOR, 24.8; 95% CI, 2.7-228.4; P = .005), and bPIs (aOR, 28.3; 95% CI, 3.4-239.4; P = .002) in PWH with Av-Adh ≤95%. Among PWH with >95% Av-Adh, there were no significant differences in the risk of VR among the different ARVs. CONCLUSIONS: These findings support the concept that dolutegravir in combination with 2 other active ARVs achieves greater virological suppression than older ARVs, including raltegravir, NNRTI, and bPI, among PWH with lower adherence.

'French LARS score': validation of the French version of the low anterior resection syndrome (LARS) score for measuring bowel dysfunction after sphincter-preserving surgery among rectal cancer patients: a study protocol.

INTRODUCTION: Many bowel problems following low anterior resection (LAR) for rectal cancer considerably impair the quality of life (QoL) of patients. The LAR syndrome (LARS) scale is a self-report questionnaire to identify and assess bowel dysfunction after rectal cancer surgery. It has been translated and validated in several languages but not in French (metropolitan French). The primary objective is to adapt the LARS scale to the French language (called French-LARS score) and to assess its psychometric properties. Secondary objectives are to assess both the prevalence and severity of LARS and to measure their impact on QoL. METHODS AND ANALYSIS: A French multicentre observational cohort study has been designed. The validation study will include translation of the LARS scale following the current international recommendations, assessment of its reliability, convergent and discriminant validities, sensitivity, internal consistency, internal validity and confirmatory analyses. One thousand patients will be enrolled for the analyses. The questionnaire will be initially administered to the first 100 patients to verify the adequacy and degree of comprehension of the questions. Then reproducibility will be investigated by a test-retest procedure in the following 400 patients.An analysis will be conducted to determine the correlation between the LARS score and the Quality of Life Questionnaire (QLQ; European Organization for Treatment and Research of Cancer's QLQ-C30, QLQ-CR29). Risk factors linked to QoL deterioration will be identified and their impact will be measured. This study will meet the need for a validated tool to improve patient care and QoL. ETHICS AND DISSEMINATION: The institutional review board of the University Hospital of Caen and the ethics committee (CPP Nord Ouest I, 25 January 2019) approved the study. TRIAL REGISTRATION NUMBER: NCT03569488.

Effect of twice-daily nevirapine on adherence in HIV-1-infected patients: a randomized controlled study.

OBJECTIVE: For optimal adherence, once-daily dosing is best. Whether this applies to antiretroviral therapy is unknown. We thus aimed to determine the effect of once-daily dosing on adherence to nevirapine. DESIGN: A three-phase (3-month observational, 4-month randomized, 5-month interventional) open-label, clinical trial at four French academic medical centres during 2005-2006 among 62 chronically HIV-1-infected subjects with long-lasting viral suppression under a twice-a-day nevirapine-based antiretroviral combination. METHODS: Adherence was measured using electronic monitoring devices and validated by sequential plasma drug levels. Participants were randomly assigned to switch to nevirapine 400 mg once-daily (n = 31) or continue nevirapine 200 mg twice-a-day (n = 31). After the randomized phase, participants had an opportunity to choose their antiretroviral dosage. Primary outcome was the mean percentage of adherence. RESULTS: Fifty-two patients qualified for electronic data analysis. During the randomized phase, the mean adherence rate was non-significantly superior by 0.5% in once-daily versus twice-a-day dosing (P = 0.68), adjusting for previous twice-a-day adherence rate (P < 0.0001). Once-daily group increased days without dose [odds ratio (OR) 1.7; 95% confidence interval (CI) 1.0, 2.8; P = 0.04], adjusting for previous drug interruptions (P < 0.0001). In the longitudinal analysis, once-daily dosing was significantly associated with at least two consecutive days without dose (OR 4.4; 95% CI 1.9, 10.3; P < 0.001). CONCLUSION: Changing from twice to once-daily nevirapine does not improve adherence. Supporting continuous adherence to antiretroviral therapy in the 'once-a-day era' remains a challenge, even if more potent regimens can achieve viral suppression at lower adherence levels.